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FRI0047 Elevated 14-3-3eta levels predict worse radiographic outcomes in patients with recent-onset inflammatory arthritis in clinical remission
  1. N Carrier1,
  2. M-P Garant2,
  3. A Marotta3,
  4. AJ De Brum Fernandes4,
  5. P Liang4,
  6. A Masetto4,
  7. Y Gui5,
  8. J Savill5,
  9. S Michienzi5,
  10. WP Maksymowych6,
  11. G Boire4
  1. 1Division of Rheumatology, CIUSSS de l'Estrie-CHUS
  2. 2Biostatistics, Centre de recherche du CHUS, Sherbrooke
  3. 3Auguex Life Sciences Crop., Vancouver
  4. 4Medicine, Division of Rheumatology, Université de Sherbrooke, Sherbrooke
  5. 5Augurex Life Sciences Corp., Vancouver
  6. 6Medicine, University of Alberta, Edmonton, Canada

Abstract

Background 14–3-3η is a joint-derived serum protein that up-regulates pro-inflammatory factors. We have previously reported that baseline 14–3-3η levels ≥0.50 ng/ml (HIGH 14–3-3η) were predictive of radiographic progression over 5 years.

Objectives Our objective was to verify if the persistence of HIGH 14–3-3η at 18 months in recent-onset polyarthritis patients in REMISSION predicts more rapid radiographic progression over the following years, up to 42 months.

Methods Serum 14–3-3η titres were assessed at baseline and at 18 months into disease, a median of 14 months after diagnosis and initiation of treatment. Three definitions of “clinical remission” at 18 months were used: Swollen Joint Count (SJC) =0; SJC + Tender Joint Count (TJC) =0; ACR/EULAR Boolean definition. The progression of radiographic damage (Erosion and Total Sharp/van der Heijde (SvH) scores) in patients with LOW (<0.50 ng/ml) or HIGH (≥0.50 ng/ml) 14–3-3η were compared using the Mann-Whitney test. P values <0.05 were considered significant.

Results Out of 331 patients, 36.0% of which had HIGH 14–3-3η at Baseline, 308 had complete data up to 5 years. Median age was 60 years, 62% women. Depending on the stringency of the definition used, variable numbers of patients reached remission at 18 months: 162 (53%) had SJC=0; 108 (35%) SJC+TJC=0; and 56 (18%) Boolean.

Remission at 18 months was negatively associated with persistence of HIGH 14–3-3η since HIGH 14–3-3η were then present in 32/162 (19.7%) SJC=0 patients; 22/108 (20.4%) SJC+TJC=0 and 13/56 (23.2%) Boolean.

Compared to patients in remission with LOW 14–3-3η, patients in remission with HIGH 14–3-3η at 18 months had numerically faster subsequent progression with all definitions. For example, in patients with Boolean remission, mean (SD) erosion progression over 42 months was 7.2±13.1 vs 1.5±3.3 and mean (SD) progression of Total score 9.2±14.5 vs 2.8±4.4 units (Figure).

However, due to low numbers and limited power, differences in progression were statistically significant only for the less strict definitions of remission and only over the following year: Erosions (SJC=0, p=0.0042, SJC+TJC=0, p=0.0236), Total score (SJC=0, p=0.0146; with a trend for SJC+TJC=0, p=0.077).

None of the comparisons over 42 months or of those involving Boolean reached significance.

Conclusions The persistence of 14–3-3η levels ≥0.50 ng/ml appears to be associated with a lower probability of reaching remission in polyarthritis patients. 14–3-3η levels ≥0.50 ng/ml in patients in clinical remission appear to be associated with more rapid radiographic (especially erosive) progression over the following year. A larger study is required to validate these findings, especially with the most stringent criterion of Boolean remission.

Disclosure of Interest N. Carrier: None declared, M.-P. Garant: None declared, A. Marotta Employee of: Augurex Life Sciences Corp., A. De Brum Fernandes Grant/research support from: AJdBF is part of the Centre de Recherche Clinique from the CHUS, which received a team grant from the Fonds de Recherche en Santé-Québec, P. Liang: None declared, A. Masetto: None declared, Y. Gui Employee of: Augurex Life Sciences Corp., J. Savill Employee of: Augurex Life Sciences Corp., S. Michienzi Employee of: Augurex Life Sciences Corp., W. Maksymowych Consultant for: Augurex Life Sciences Corp., G. Boire Grant/research support from: GB is part of the Centre de Recherche Clinique from the CHUS, which received a team grant from the FRSQ. GB is the recipient of CIHR grant MOP-110959. Since 2007, the Sherbrooke EUPA cohort has also received financial support from the Canadian ArTritis CoHort (CATCH), a study designed and implemented by investigators and financially supported via unrestricted research grants initially by Amgen Canada Inc

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